{"uniprot":"Q8NGS5","gene":"OR13C4","name":"Olfactory receptor 13C4","organism":"Homo sapiens (Human)","status":"dark","length":318,"sequence":"MDKINQTFVREFILLGLSGYPKLEIIFFALILVMYVVILIGNGVLIIASILDSRLHMPMYFFLGNLSFLDICYTTSSIPSTLVSLISKKRNISFSGCAVQMFFGFAMGSTECFLLGMMAFDRYVAICNPLRYPIIMNKVVYVLLTSVSWLSGGINSTVQTSLAMRWPFCGNNIINHFLCEILAVLKLACSDISVNIVTLAVSNIAFLVLPLLVIFFSYMFILYTILRTNSATGRHKAFSTCSAHLTVVIIFYGTIFFMYAKPKSQDLLGKDNLQATEGLVSMFYGVVTPMLNPIIYSLRNKDVKAAIKYLLSRKAINQ","function_summary":"A human chemosensory G protein-coupled receptor that resides predominantly at the plasma membrane and detects small volatile ligands to initiate signal transduction. Ligand binding to the extracellular face of its seven-helix bundle activates heterotrimeric G proteins, elevates cyclic nucleotide signaling, and drives downstream pathways that can modulate transcriptional programs. Its multi-pass membrane architecture explains stable cell-surface localization, while signaling crosstalk accounts for a minor nucleoplasmic pool linked to gene-regulatory responses.","plain_language":"OR13C4 has barely been studied. The model's best guess: A human chemosensory G protein-coupled receptor that resides predominantly at the plasma membrane and detects small volatile ligands to initiate signal transduction. Ligand binding to the extracellular face of its seven-helix bundle activates heterotrimeric G proteins, elevates cyclic nucleotide signaling, and drives downstream pathways that can modulate transcriptional programs.","uniprot_summary":"Odorant receptor.","go_terms":{"molecular_function":[{"id":"GO:0004984","label":"olfactory receptor activity"}],"biological_process":[{"id":"GO:0006355","label":"regulation of DNA-templated transcription"}],"cellular_component":[{"id":"GO:0005886","label":"plasma membrane"},{"id":"GO:0005654","label":"nucleoplasm"}]},"interpro":[{"id":"IPR017452","name":"GPCR, rhodopsin-like, 7TM","type":"domain","start":41,"end":296},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":26,"end":50},{"id":"IPR000725","name":"Olfactory receptor","type":"family","start":33,"end":314},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":59,"end":80},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":104,"end":126},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":199,"end":222},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":278,"end":304}],"reasoning":"I begin with the InterPro architecture. The core transmembrane engine is IPR017452 (GPCR, rhodopsin-like, 7TM domain, residues 41–296), which encodes the canonical seven-helix bundle that transduces extracellular ligand binding into intracellular G protein activation. This structural core is flanked and reinforced by multiple olfactory/rhodopsin-like GPCR family signatures: IPR000276 (G protein-coupled receptor, rhodopsin-like family) appears in several internal windows—[26–50], [59–80], [104–126], [199–222], and [278–304]—marking conserved motifs across the N-terminus and intracellular loops that coordinate G protein coupling and arrestin-mediated desensitization. The presence of IPR000725 (Olfactory receptor family, residues 33–314) specifies the chemosensory subclass that binds volatile odorants and preferentially couples to the olfactory G protein. The ordered layout—an N-terminal extracellular region feeding into a 7TM bundle and internal rhodopsin-like motifs—causally establishes a chemoreceptive GPCR that detects small hydrophobic ligands and triggers intracellular signaling.\n\nThis architecture dictates the molecular function formalized as GO:0004984 olfactory receptor activity. The seven-helix bundle and olfactory-family signatures cause odorant binding at the extracellular face and conformational switching that activates heterotrimeric G proteins. The GPCR mechanism naturally links to broader signaling cascades that modulate gene expression programs; thus, receptor-driven pathways can regulate transcriptional outputs, aligning with GO:0006355 regulation of DNA-templated transcription. In olfactory neurons and other sensory cells, GPCR activation elevates cAMP and engages downstream kinases and transcriptional regulators; this signaling-to-transcription axis provides a mechanistic route by which receptor activity influences gene expression.\n\nCellular localization follows directly from the 7TM design and the olfactory receptor class. The hydrophobic bundle and multi-pass topology anchor the protein in the plasma membrane, consistent with GO:0005886 plasma membrane and the experimentally supported designation as a cell membrane, multi-pass membrane protein. A nucleoplasmic pool (GO:0005654 nucleoplasm) can be rationalized by receptor trafficking and signaling crosstalk: a fraction of GPCRs and their complexes transiently associate with nuclear-proximal compartments via soluble fragments or signaling hubs that relay activity states to transcriptional machinery. Such dynamics are compatible with the receptor’s transcriptional regulatory influence.\n\nMechanistically, odorant binding stabilizes an active GPCR conformation that recruits and activates the olfactory G protein (Golf), stimulating adenylyl cyclase and cAMP production. Elevated cAMP opens cyclic nucleotide-gated channels and can feed into kinase pathways that ultimately tune transcriptional networks. I therefore hypothesize interactions with Golf (GNAL), adenylyl cyclase 3, Gβγ subunits, β-arrestins, and receptor-transport machinery (RTP/REEP chaperones). Together, these partners enable membrane residency, signal propagation, and transcriptional coupling that together define olfactory receptor function and its downstream gene-regulatory effects.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q8NGS5.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q8NGS5"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q8NGS5/entry","atlas":"/p/Q8NGS5"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}